Role of per- and polyfluoroalkyl substances in the cardiorenal system: Unraveling crosstalk from the network of pollutants and phenotypes.

Although per- and polyfluoroalkyl substances (PFAS) have been frequently linked to cardiovascular and renal disease separately, evidence remains scarce regarding their systematic effect. Therefore, we recruited 546 newly diagnosed acute coronary syndrome (ACS) patients and detected seven myocardial enzymes and six kidney function biomarkers. Twelve PFAS were also assessed with ultra-high-performance liquid chromatography-tandem mass spectrometry. Generalized linear model and restricted cubic spline model were applied to single pollutant analysis. Quantile g-computation was used for mixture analysis. Network model was utilized to identify central and bridge nodes of pollutants and phenotypes. In the present study, perfluorohexane sulfonic acid was positively associated with uric acid (UA) (ß= 0.04, 95% confidence interval (CI): 0.01, 0.07), and perfluorobutanoic acid was negatively associated with estimated glomerular filtration rate (ß= -0.04, 95% CI: -0.07, -0.01) but positively associated with UA (ß= 0.03, 95% CI: 0.01, 0.06). In mixture analysis, each quantile increase in the PFAS mixture was significantly associated with UA (ß= 0.08, 95% CI: 0.04, 0.11). Network analysis revealed that perfluorooctanoate, UA, and myoglobin were denoted as bridge nodes, and the first principal component of lactate dehydrogenase and creatine kinase- myocardial band was identified as the node with the highest strength and expected influence. This study investigates the systematic impact of PFAS exposure through cardiorenal interaction network, which highlights that PFAS may serve as an upstream approach in UA-modulated cardiorenal network to affect cardiorenal system comprehensively.

Longitudinal frailty assessment in the prediction of survival among patients with advanced chronic kidney disease: a prospective observational single-centre cohort study.

OBJECTIVES: This study aims to describe the prevalence, characteristics and longitudinal changes in frailty among outpatient chronic kidney disease (CKD) and haemodialysis (HD) populations and their impact on survival. DESIGN: Prospective observational cohort study. SETTING: Single-centre ambulatory tertiary care setting, metropolitan Australian teaching hospital. PARTICIPANTS: Adult patients with advanced CKD (defined as estimated glomerular filtration rate <20 mL/min) or undergoing maintenance HD. Consent model was informed opt-out consent. INTERVENTIONS: Fried frailty assessment at baseline, 6 months and 12 months of longitudinal follow-up. PRIMARY OUTCOMES: All-cause mortality and kidney transplantation events. RESULTS: Frailty was identified in 36.3% of the 256 participants, while an additional 46.5% exhibited prefrailty. Frailty was equally common among CKD and HD cohorts. Frailty outperformed age, comorbidity and laboratory parameters in predicting mortality risk with HR 2.83 (95% CI 1.44 to 5.56, p<0.001). Frailty also substantially reduced access to transplantation. While most participants exhibited static Fried phenotype over longitudinal assessment, improvements in frailty were observed as frequently as frailty progression. Female gender and symptom burden predicted frailty progression. CONCLUSIONS: Frailty is highly prevalent and closely aligned with survival outcomes. Frailty among patients attending routine outpatient care may demonstrate responsiveness to intervention with subsequent improvements in mortality and other patient-level outcomes.

Kidney function in newly diagnosed myeloma patients: factors associated with kidney impairment and recovery.

Kidney disease is a common complication of multiple myeloma (MM) and a risk factor for increased morbimortality. In this retrospective cohort study based on medical records, we analyzed the kidney function of patients with renal disease related to MM during the first year of treatment. All patients included were consecutively admitted to the outpatient services of two hospitals between January 2009 and January 2019 and met the diagnostic criteria for MM regardless of the reason for seeking medical help. We excluded patients who had kidney disease or who were on dialysis before MM diagnosis. We investigated the factors associated with renal function recovery using multivariate analysis. We evaluated 167 patients (median age of 66 ± 11.49 years). Almost half of the patients had arterial hypertension (76; 45.5%). The majority had International Staging System (ISS) grades 3 (73; 43.7%) or 2 (60; 35.9%). Seventy-four (44%) patients had an estimated glomerular filtration rate (eGFR) < 60 ml/min/1.73 m² at the time of MM diagnosis. Fifty-two patients (31%) underwent hematopoietic stem cell transplantation (HSCT). After 12 months, 4 (2.3%) patients needed dialysis, and 18 (10.7%) died. The factors associated with an eGFR < 60 ml/min/1.73 m² were anemia, hyperuricemia, 24-hour proteinuria > 1.0 g, and extramedullary plasmacytoma. However, only baseline renal function (eGFR > 60 ml/min/1.73 m2) and HSCT were associated with greater recovery of renal function at 12 months of follow-up.

Association between early exposure to famine and risk of renal impairment in adulthood: a systematic review and meta-analysis.

Malnutrition early in life increases the later-life risk of noncommunicable diseases, and previous epidemiologic studies have found a link between famine and renal impairment, but no consensus has been reached. This meta-analysis and systematic review were conducted to assess the correlation between early-life famine exposure and the risk of developing renal impairment. Search in Embase, Scopus, Web of Science, PubMed, and Cochrane using keywords that report the correlation between early famine exposure and renal function indicators. RevMan and Stata software were used for data analysis. This meta-analysis contained twelve observational studies. The findings demonstrated a link between prenatal famine exposure and a higher risk of developing chronic kidney disease (CKD) (odds ratio (OR) = 1.73, 95% confidence interval (CI): 1.25, 2.39), a decreased estimated glomerular filtration rate (eGFR) (mean difference (MD) = -10.05, 95% CI: -11.64, -8.46), and increased serum creatinine (Scr) (MD = 0.02, 95% CI: 0.01, 0.03) compared to unexposed individuals. Famine exposure in childhood was associated with decreased eGFR (MD = -9.43, 95% CI: -12.01, -6.84) and increased Scr (MD = 0.03, 95% CI: 0.01, 0.04), but not with CKD (OR = 0.980, 95% CI: 0.53, 1.81). Famine exposure in adolescence and adulthood was associated with decreased eGFR (MD = -20.73, 95% CI: -22.40, -19.06). Evidence certainty was deemed to be of low or extremely low quality. Famine exposure early in life could pose a greater risk of developing renal impairment in adulthood, but this outcome may be driven by uncontrolled age differences between famine-births and post-famine-births (unexposed).

Do Parenteral Iron Therapies Preserve or Deteriorate Kidney Functions? "Iron Carboxy Maltose or Iron Sucrose?"

BACKGROUND: Treatment of end stage renal disease (ESRD) is based on preserving renal functions. Since renal anemia is frequently detected, we use parenteral iron treatments in patients with chronic kidney disease (CKD). However, there need to be more precise and sufficient studies on the effect of these treatments on the rate of decrease in the glomerular filtration rate (GFR). Therefore, we conducted a study comparing the rates of change in renal function in patients who had used parenteral iron for at least five years. METHODS: Our study is a retrospective cohort study, and 180 patients with CKD (86 women, 94 men, mean age: 63.5 ± 11.4 years) who had been followed and treated in nephrology outpatient clinics for at least five years and met the study criteria were included in the study. Patients were divided into three groups for iron therapy: not receiving iron therapy, iron carboxy maltose (ICM), and iron sucrose (IS) parenterally. Each group consisted of 60 people. The first and last creatinine and GFR values were compared for a 5-year follow-up in each group. RESULTS: There was no significant difference between the two groups, those using and those not using iron, regarding creatinine increase and GFR decrease rate. Additionally, no significant difference was detected in the GFR decline rates of patients using ICM and IS. CONCLUSIONS: This study reduces the concerns that correcting anemia through parenteral iron therapy in patients with CKD may harm renal function.

Association between kidney function, frailty and receipt of invasive management after acute coronary syndrome.

BACKGROUND: Reduced estimated glomerular filtration rate (eGFR) is associated with lower use of invasive management and increased mortality after acute coronary syndrome (ACS). The reasons for this are unclear. METHODS: A retrospective clinical cohort study was performed using data from the English National Institute for Health Research Health Informatics Collaborative (2010-2017). Multivariable logistic regression was used to investigate whether eGFR<90 mL/min/1.73 m2 was associated with conservative ACS management and test whether (a) differences in care could be related to frailty and (b) associations between eGFR and mortality could be related to variation in revascularisation rates. RESULTS: Among 10 205 people with ACS, an eGFR of <60 mL/min/1.73m2 was found in 25%. Strong inverse linear associations were found between worsening eGFR category and receipt of invasive management, on a relative and absolute scale. People with an eGFR <30 mL compared with ≥90 mL/min/1.73 m2 were half as likely to receive coronary angiography (OR 0.50, 95% CI 0.40 to 0.64) after non-ST-elevation (NSTE)-ACS and one-third as likely after STEMI (OR 0.30, 95% CI 0.19 to 0.46), resulting in 15 and 17 per 100 fewer procedures, respectively. Following multivariable adjustment, the ORs for receipt of angiography following NSTE-ACS were 1.05 (95% CI 0.88 to 1.27), 0.98 (95% CI 0.77 to 1.26), 0.76 (95% CI 0.57 to 1.01) and 0.58 (95% CI 0.44 to 0.77) in eGFR categories 60-89, 45-59, 30-44 and <30, respectively. After STEMI, the respective ORs were 1.20 (95% CI 0.84 to 1.71), 0.77 (95% CI 0.47 to 1.24), 0.33 (95% CI 0.20 to 0.56) and 0.28 (95% CI 0.16 to 0.48) (p<0.001 for linear trends). ORs were unchanged following adjustment for frailty. A positive association between the worse eGFR category and 30-day mortality was found (test for trend p<0.001), which was unaffected by adjustment for frailty. CONCLUSIONS: In people with ACS, lower eGFR was associated with reduced receipt of invasive coronary management and increased mortality. Adjustment for frailty failed to change these observations. Further research is required to explain these disparities and determine whether treatment variation reflects optimal care for people with low eGFR. TRIAL REGISTRATION NUMBER: NCT03507309.

Outpatient Renal Function Screening Before Contrast-Enhanced CT Examinations.

Intravascular administration of iodinated contrast media can cause contrast-induced acute kidney injury, especially in patients with an estimated glomerular filtration rate (eGFR) less than 30 mL/min/1.73 m². The American College of Radiology (ACR) and the European Society of Urogenital Radiology (ESUR) guidelines recommend renal function screening based on medical history, but their effectiveness has been under-evaluated. This retrospective study included 2,560 consecutive adult outpatients without eGFR measurements within 180 days before contrast-enhanced computed tomography (CT) at a single tertiary hospital from July through September 2023. On the day of CT, they underwent eGFR tests and 1.1% had an eGFR < 30 mL/min/1.73 m², preferentially with histories of gout and renal disease. According to the ACR and ESUR strategies, 16.9% and 38.8% of all study participants were positive, respectively, identifying 92.6% and 96.3% of patients with renal insufficiency. Both strategies demonstrated high negative predictive values. These results support selective renal function screening before contrast-enhanced examinations.

Persistent Renal Dysfunction After Acute Kidney Injury Among STEMI Patients Undergoing Primary Coronary Intervention: Prevalence and Predictors.

BACKGROUND: Acute kidney injury (AKI) is a common and serious complication of ST-elevation myocardial infarction (STEMI). AKI and chronic kidney disease (CKD) are highly heterogeneous, leaving a wide gap between them. Therefore, the term acute kidney disease (AKD) was implemented, describing prolonged renal injury between 7 and 90 days. We aimed to evaluate the prevalence and predictors of AKD among STEMI patients. METHODS: This retrospective observational study included 2940 consecutive patients admitted with STEMI between 2008 and 2022. Renal function was assessed upon admission and routinely thereafter. Renal outcomes were evaluated according to KDIGO criteria, with AKD defined as persistent renal injury of between 7 and 90 days. RESULTS: Two hundred and fifty-two subjects with STEMI and AKI were included; of them, 117 (46%) developed AKD. Among baseline CKD patients, higher rates of AKD were observed (60% vs. 46%). KDIGO index ≥ 2 was an independent predictor for AKD in in subjects without baseline CKD (AOR 2.63, 95% CI 1.07-6.53). In subjects with baseline CKD, older age and higher creatinine were independent predictors for AKD. Subjects with AKD had a higher 1-year mortality rate (HR 3.39, 95% CI 1.71-6.72, p < 0.01). This trend was mainly driven by the CKD subpopulation where higher mortality rates for AKD on CKD were observed (HR 5.26, 95% CI 1.83-15.1, p < 0.01). CONCLUSION: AKD is common among STEMI patients with AKI. The presence of CKD and higher KDIGO stage should prompt strict monitoring for early diagnosis, treatment, and prevention of renal function deterioration.

Urinary cyclophilin A as an early marker of chronic kidney disease with underlying type 2 diabetes.

Cyclophilin A (CypA) is a novel renal inflammation biomarker, with levels altered in various diseases, particularly in patients with diabetes mellitus (DM) and kidney damage. This study aimed to investigate the correlation between urinary cyclophilin A (uCypA) and chronic kidney disease (CKD) conditions with and without type 2 diabetes mellitus (T2DM) using an in-house enzyme-linked immunoassay (ELISA) method. A uCypA strip-test prototype was also developed. An indirect ELISA was performed to determine the uCypA levels. A 0.48 µg/mL uCypA cutoff differentiated healthy patients from those with early-stage CKD (stages I and II). The uCypA levels were significantly increased in patients with progression of renal deterioration, especially in the T2DM with late-stage CKD group, compared to the control group. Fasting blood sugar (FBS), estimated glomerular filtration rate (eGFR), albumin/creatinine ratio, and metformin use were associated with uCypA levels. Multinomial logistic regression analysis revealed an association between uCypA levels and T2DM diagnosed for over five years and early-stage CKD. This finding shows that uCypA could be used as a biomarker for distinguishing early-stage CKD as well as T2DM complications, which is beneficial for patients to be aware of their health status and change their behavior to slow kidney deterioration.

Association of urinary albumin excretion with all-cause and cardiovascular mortality among patients with rheumatoid arthritis: a national prospective study.

Background: Rheumatoid arthritis (RA) patients suffering from chronic renal insufficiency tend to exhibit subtle manifestations at the beginning. Urine albumin to creatinine ratio (ACR) is a sensitive indicator for early assessment of renal function. However, it is unclear whether it serves as an independent risk factor influencing the prognosis of RA patients. Methods: National Health and Nutrition Examination Survey (NHANES) data from 2009-2018 were included. Kaplan-Meier (K-M) curves were plotted to compare the cumulative survival probability of RA patients with different urinary albumin excretion. The association of ACR with mortality among RA patients was investigated with Cox regression model, restricted cubic spline (RCS) and stratified analyses. The prognostic efficacy of ACR and estimated glomerular filtration rate (eGFR) was evaluated by receiver operating characteristic (ROC) curves. Results: The Cox regression model adjusted with covariates showed a 53% (HR 1.53, 95% CI 1.06-2.21) increase in all-cause mortality and a statistically non-significant increase in cardiovascular disease (CVD) mortality in RA patients with microalbuminuria (30mg/g ≤ACR<300mg/g). ACR≥300mg/g was associated with an increase in all-cause mortality (HR 2.62, 95% CI 1.55-4.45) and CVD mortality (HR 5.67, 95% CI 1.96-16.39). RCS demonstrated a nonlinear correlation between ACR and all-cause mortality in RA patients with microalbuminuria. Subgroup analysis showed that CVD mortality was higher in RA patients with microalbuminuria characterized by the following features: female, other ethnicity, eGFR≥60 ml/min/1.73 m2, hypertension or hyperlipidemia. Compared with eGFR, ACR provided better prognostic efficacy than eGFR with higher values of the area under the curve (AUC) for all-cause mortality (AUC=0.683, 95% CI 0.613-0.754) and CVD mortality (AUC=0.681, 95% CI 0.541-0.820). Conclusion: ACR is an independent risk factor affecting the prognosis of RA patients. The all-cause mortality was increased in RA patients with albuminuria. There was an upward trend in the CVD mortality of those with macroalbuminuria when ACR increased.

The renal histopathology of nonproteinuric kidney impairment: a three center experience.

Proteinuria is a biomarker of kidney injury that typically results from glomerular and/or tubulointerstitial disease. Whereas kidney impairment with normal urinary protein excretion is usually less focused and understudied. We conducted a retrospective review of the renal histopathology of the patients with variable degrees of unexplained renal insufficiency but with normal range proteinuria between 2014 and 2024 of  three university teaching hospitals in Shenzhen city of Southern  China. Patients with kidney dysfunction of undetermined or uncertain etiology and with normal urinary protein excretion (defined by a 24hr urinary protein excretion < 150 mg or spot urinary protein to creatinine ratio [PCR] < 150 mg/g) were enrolled and analyzed. In a total of 2405 patients, 53 (2.2%) fulfilled the inclusion criteria  (male/female 40/13, age 47.3 ± 14.3 years) with a mean eGFR of 46.6 ± 16.8 ml/min per 1.73 m2. Glomerular disease (GD) was the most frequent pathological finding identified in 23 (43.4%) patients, while 19 (35.8%) cases  showed tubulointerstitial disease (TID) and 11 (20.8%) patients exhibited small vascular disease (SVD). Patients in the TID had the lowest mean eGFR and the highest numerical 24hr urinary protein excretion among the three groups. The incidence of acute kidney injury was significantly higher in TID than in other two groups. The patients in the SVD group had the highest fraction of underlying hypertension. Kidney dysfunction with normal range proteinuria may be related with, in descending order of probablity,  glomerular, tubulointerstitial and small vascular diseases. Renal biopsies were proved useful in informing therapeutic choice, long-term management and in predicting prognosis in this setting.

Association of dietary antioxidant indices with kidney function indicators in patients with type 2 diabetes: a cross-sectional study.

This cross-sectional study investigated the relationship between dietary antioxidant indices and kidney function indicators in 240 outpatient adults with type 2 diabetes. Dietary intake was assessed using three 24-h dietary recalls. Dietary total antioxidant capacity (DTAC), dietary antioxidant index (DAI), and dietary antioxidant quality score (DAQS) were obtained. Indicators of kidney function, including serum creatinine, urea, blood urea nitrogen (BUN), and glomerular filtration rate (GFR), were extracted from medical records. After adjustment, the highest DAI tertile had lower serum creatinine (0.98 ± 0.27 vs 1.03 ± 0.32 mg/dL, P < 0.001), reduced urea (30.97 ± 8.75 vs 34.07 ± 14.45 mg/dL, P = 0.005), and higher GFR (85.16 ± 29.43 vs 74.16 ± 22.18 ml/min per 1·73 m2, P < 0.001) compared to the lowest tertile. The results of logistic regression analysis indicated a borderline significant inverse association of serum urea > 20 mg/dl with DTAC (odds ratio (OR):0.28; 95% CI: 0.07-1.09; Ptrend = 0.06). Multivariable linear regression analysis revealed a significant aligned correlation between DAQs and GFR (ß: 0.20; P-value: 0.005) and a marginally significant direct relationship between DAI and GFR (ß: 0.14; P-value: 0.06). However, no significant association was observed for DTAC with GFR (ß:-0.02; P-value: 0.80). Diets with higher antioxidant capacity may be linked to improved kidney function in type 2 diabetes but our results did not support this strongly.

Glucagon-like peptide-1 receptor agonists and kidney outcomes.

Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have gained increasing attention for their potential benefits in people with type 2 diabetes mellitus (T2DM) with chronic kidney disease (CKD). Most supportive evidence of a kidney-protective effect of the GLP-1RA class of medications has been derived from kidney-related outcomes reported from cardiovascular outcome trials (CVOTs). GLP-1RAs have been shown to reduce albuminuria, mitigate cardiovascular risk, and possibly attenuate estimated glomerular filtration rate (eGFR) decline. The kidney-protective effects of GLP-1RAs are thought to be attributed to their anti-inflammatory, antioxidant, and vasodilatory properties. Despite these promising findings, the use of GLP-RAs has yet to be definitively shown to slow progression to chronic kidney failure in people with T2DM. The Research Study to See How Semaglutide Works Compared to Placebo in People With Type 2 Diabetes and Chronic Kidney Disease (FLOW trial) is the first major trial assessing the potential of a GLP-1RA to slow progression of kidney disease in people with established CKD to clinically important kidney end points. On March 5, 2024, the top line result from FLOW was announced with semaglutide 1.0 mg being reported to reduce the primary end point of the trial by a significant 24% compared with placebo. Here, we summarize the kidney outcomes reported from CVOTs for the GLP-1RA class of medication and briefly describe kidney outcomes from other major GLP-1RAs trials. We also discuss a potential role of the dual GLP-1/glucose-dependent insulinotropic polypeptide (GIP) receptor agonist, tirzepatide, as a kidney-protective agent.

Reexamining Transplant Outcomes in Acute Kidney Injury Kidneys Through Machine Learning.

BACKGROUND: Despite many people awaiting kidney transplant, kidney allografts from acute kidney injury (AKI) donors continue to be underutilized. We aimed to cluster kidney transplant recipients of AKI kidney allografts using an unsupervised machine learning (ML) approach. METHODS: Using Organ Procurement and Transplantation Network-United Network for Organ Sharing (OPTN/UNOS) data, a consensus clustering cohort analysis was performed in 12 356 deceased donor kidney transplant recipients between 2015 and 2019 in whom donors had a terminal serum creatinine ≥1.5 mg/dL. Significant cluster characteristics were determined, and outcomes were compared. RESULTS: The median donor terminal creatinine was 2.2 (interquartile range [IQR] 1.7-3.3) mg/dL. Cluster analysis was performed on 12 356 AKI kidney recipients, and three clinically distinct clusters were identified. Young, sensitized kidney re-transplant patients characterized Cluster 1. Cluster 2 was characterized by first-time kidney transplant patients with hypertensive and diabetic kidney diseases. Older diabetic recipients characterized Cluster 3. Clusters 1 and 2 donors were young and met standard kidney donor profile index (KDPI) criteria; Cluster 3 donors were older, more likely to have hypertension or diabetes, and meet high KDPI criteria. Cluster 1 had a higher risk of acute rejection, 3-year patient death, and graft failure. Cluster 3 had a higher risk of death-censored graft failure, patient death, and graft failure at 1 and 3 years. Cluster 2 had the best patient-, graft-, and death-censored graft survival at 1 and 3 years. Compared to non-AKI kidney recipients, the AKI clusters showed a higher incidence of delayed graft function (DGF, AKI: 43.2%, 41.7%, 45.3% vs. non-AKI: 25.5%); however, there were comparable long-term outcomes specific to death-censored graft survival (AKI: 93.6%, 93.4%, 90.4% vs. non-AKI: 92.3%), patient survival (AKI: 89.1%, 93.2%, 84.2% vs. non-AKI: 91.2%), and overall graft survival (AKI: 84.7%, 88.2%, 79.0% vs. non-AKI: 86.0%). CONCLUSIONS: In this unsupervised ML approach study, AKI recipient clusters demonstrated differing, but good clinical outcomes, suggesting opportunities for transplant centers to incrementally increase kidney utilization from AKI donors.

Prediction of Renal Graft Function 1 Year After Adult Deceased-Donor Kidney Transplantation Using Variables Available Prior to Transplantation.

BACKGROUND Kidney transplantation is still the best therapy for patients with end-stage renal disease, but the demand for donor organs persistently surpasses the supply. A prognostic model using pre-transplant data for the prediction of renal graft function would be helpful to optimize organ allocation and avoid futile transplantations. MATERIAL AND METHODS Retrospective data of 2431 patients who underwent kidney transplantation between January 01, 2000, and December 31, 2012 with subsequent ten-year clinical follow-up in our transplant center were analyzed. Of these, 1172 patients met the inclusion criteria. Multivariable regression modelling was used to develop a prognostic model for the prediction of graft function after 1 year utilizing only pre-transplant data. The final model was assessed with the area under the receiver operating characteristic (AUROC) curve. RESULTS Donor age, donor serum creatinine, recipient body mass index, re-transplantations beyond the second kidney transplantation, and cold ischemia time had an independent, significant influence on graded renal graft function 1 year after kidney transplantation. AUROC analysis of the prognostic model was >0.700 for all GFR categories except KDIGO G5, indicating high sensitivity and specificity of prediction. CONCLUSIONS For improvement of renal graft function, organs from older donors or donors with high serum creatinine should not be used in obese recipients and for re-transplantations beyond the second one. Cold ischemia time should be as short as possible.

Evaluation of cardiac remodeling in pediatric chronic kidney disease by cardiovascular magnetic resonance.

BACKGROUND: Children with chronic kidney disease (CKD) are at high risk of cardiovascular disease. Cardiovascular magnetic resonance (CMR) is the reference method for assessing cardiac remodeling. To our knowledge, no study has reported a comprehensive analysis of left ventricular(LV) cardiac remodeling using CMR in different stages of pediatric CKD. This prospective case-control study aimed to investigate cardiac remodeling in pediatric CKD, using CMR, and determine its relationship with risk factors. METHOD: CMR was performed in 124 children with CKD and 50 controls. The cardiac remodeling parameters included left ventricular mass index (LVMI), LV remodeling index (LVRI), and LV wall thickness. Univariable and multivariable analyses were performed to assess the cardiac remodeling risk factors. RESULTS: Cardiac remodeling was observed in 35.5% (44/124) of children with CKD. The LVMI, LVRI, and LV wall thickness were higher in advanced stages of CKD (P < 0.05). In the CKD stage 1-2 group, a lower in the estimated glomerular filtration rate was an independent determinant of impaired LVMI (ß = -0.425, P = 0.019) and LVRI (ß = -0.319, P = 0.044). A higher protein to creatinine ratio(PCR) was independently associated with impaired LVRI (ß = 0.429, P = 0.022). In the CKD stage 3-5 group, higher in systolic blood pressure (SBP) (ß = 0.464, P = 0.005) and PCR (ß = 0.852, P = 0.031) were independent determinants of impaired LVMI. Additionally, higher SBP was positively correlated with impaired LVRI(r = 0.599, P < 0.001). There was a trend toward more abnormal cardiac remodeling in the CKD stage 3-5 group with hypertension than those without. CONCLUSION: Cardiac remodeling is prevalent in children with CKD, from an early stage. kidney markers are independently associated with cardiac remodeling. Hypertension increases the risk of cardiac remodeling in CKD stages 3-5. Strict BP control may help reverse or prevent remodeling.

Observational study of immunosuppressive treatment patterns and outcomes in primary membranous nephropathy: a multicenter retrospective analysis.

BACKGROUND: We evaluated the efficacy of different immunosuppressive regimens in patients with primary membranous nephropathy in a large national cohort. METHODS: In this registry study, 558 patients from 47 centers who were treated with at least one immunosuppressive agent and had adequate follow-up data were included. Primary outcome was defined as complete (CR) or partial remission (PR). Secondary composite outcome was at least a 50% reduction in estimated glomerular filtration (eGFR), initiation of kidney replacement therapies, development of stage 5 chronic kidney disease, or death. RESULTS: Median age at diagnosis was 48 (IQR: 37-57) years, and 358 (64.2%) were male. Patients were followed for a median of 24 (IQR: 12-60) months. Calcineurin inhibitors (CNIs) with or without glucocorticoids were the most commonly used regimen (43.4%), followed by glucocorticoids and cyclophosphamide (GC-CYC) (39.6%), glucocorticoid monotherapy (25.8%), and rituximab (RTX) (9.1%). Overall remission rate was 66.1% (CR 26.7%, PR 39.4%), and 59 (10.6%) patients reached secondary composite outcome. Multivariate logistic regression showed that baseline eGFR (OR 1.011, 95% CI: 1.003-1.019, p = 0.007), serum albumin (OR 1.682, 95% CI: 1.269-2.231, p < 0.001), and use of RTX (OR 0.296, 95% CI: 0.157-0.557, p < 0.001) were associated with remission rates; whereas only lower baseline hemoglobin was significantly associated with secondary composite outcome (OR: 0.843, 95% CI: 0.715-0.993, p = 0.041). CYC use was significantly associated with higher remission (OR 1.534, 95% CI: 1.027-2.290, p = 0.036). CONCLUSIONS: Higher baseline eGFR and serum albumin levels correlated with increased remission rates. Remission rates were lower in patients treated with RTX, while those on GC-CYC showed higher rates of remission. Due to the study's retrospective nature and multiple treatments used, caution is warranted in interpreting these findings.

Glomerular filtration rate determined by measuring serum clearance of iohexol in unanesthetized cheetahs (Acinonyx jubatus) with comparison to serum symmetric dimethylarginine.

One of the more common diseases affecting zoo-managed cheetahs (Acinonyx jubatus) is chronic renal disease, which can impact their welfare and ultimately shortens their lifespan. Early diagnosis, for which estimating Glomerular Filtration Rate (GFR) is one such tool, is imperative to help mitigate the negative impacts of this insidious disease. GFR was determined by measuring the serum clearance of iohexol in nine clinically normal, cheetahs managed under human care that presented for voluntary blood collection. A 2-sample iohexol clearance method was performed, along with serum symmetric dimethylarginine (SDMA) determination. SDMA has shown promise in humans, dogs, and cats, as an early biomarker of renal disease. Additionally, the relationship between GFR and SDMA, along with serum creatinine and BUN were analyzed. The mean values for the uncorrected GFR and corrected GFR were 2.08 ± 0.215 mL/min/kg body weight and 1.87 ± 0.173 mL/min/kg body weight, respectively. No significant correlations were observed between GFR, SDMA, serum creatinine, or BUN. Both the uncorrected and corrected iohexol-based GFR values were similar to an inulin-based GFR reference interval determined in zoo managed cheetahs and a reported domestic cat iohexol-based GFR reference interval. Serum SDMA values support previous research suggesting cheetahs have a separate reference interval from domestic cats (0-14 µg/dL). Measuring GFR by the serum clearance of iohexol shows promise as a readily available, cheap, and easily administered clearance marker that can be used in cheetahs trained for voluntary blood collection, thereby avoiding the need for anesthesia.

Creatinine clearance/eGFR ratio: a simple index for muscle mass related to mortality in ICU patients.

INTRODUCTION: In patients admitted to the intensive care unit (ICU), muscle mass is inversely associated with mortality. Although muscle mass can be estimated with 24-h urinary creatinine excretion (UCE), its use for risk prediction in individual patients is limited because age-, sex-, weight- and length-specific reference values for UCE are lacking. The ratio between measured creatinine clearance (mCC) and estimated glomerular filtration rate (eGFR) might circumvent this constraint. The main goal was to assess the association of the mCC/eGFR ratio in ICU patients with all-cause hospital and long-term mortality. METHODS: The mCC/eGFR ratio was determined in patients admitted to our ICU between 2005 and 2021 with KDIGO acute kidney injury (AKI) stage 0-2 and an ICU stay ≥ 24 h. mCC was calculated from UCE and plasma creatinine and indexed to 1.73 m2. mCC/eGFR was analyzed by categorizing patients in mCC/eGFR quartiles and as continuous variable. RESULTS: Seven thousand five hundred nine patients (mean age 61 ± 15 years; 38% female) were included. In-hospital mortality was 27% in the lowest mCC/eGFR quartile compared to 11% in the highest quartile (P < 0.001). Five-year post-hospital discharge actuarial mortality was 37% in the lowest mCC/eGFR quartile compared to 19% in the highest quartile (P < 0.001). mCC/eGFR ratio as continuous variable was independently associated with in-hospital mortality in multivariable logistic regression (odds ratio: 0.578 (95% CI: 0.465-0.719); P < 0.001). mCC/eGFR ratio as continuous variable was also significantly associated with 5-year post-hospital discharge mortality in Cox regression (hazard ratio: 0.27 (95% CI: 0.22-0.32); P < 0.001). CONCLUSIONS: The mCC/eGFR ratio is associated with both in-hospital and long-term mortality and may be an easily available index of muscle mass in ICU patients.

Association between inflammatory biomarkers and postoperative acute kidney injury after cardiac surgery in patients with preoperative renal dysfunction: a retrospective pilot analysis.

BACKGROUND: Acute kidney injury (AKI) represents a significant post-cardiac surgery complication, particularly prevalent among individuals with pre-existing renal dysfunction. Chronic kidney disease (CKD) is frequently accompanied by persistent, low-grade inflammation, which is known to exacerbate systemic stress responses during surgical procedures. This study hypothesizes that these inflammatory responses might influence the incidence and severity of postoperative acute kidney injury (AKI), potentially serving as a protective mechanism by preconditioning the kidney to stress. METHODS: This retrospective study enrolled patients with preoperative renal dysfunction (eGFR between 15 and 60 ml/min/1.73 m²) who underwent cardiac surgery between January 2020 and December 2022. Preoperative inflammatory biomarkers were evaluated. The primary outcome was the incidence of postoperative AKI, as defined by the Kidney Disease: Improving Global Outcomes (KDIGO) criteria. Multivariate regression models and sensitivity analyses were conducted to ascertain the relationship between inflammatory biomarkers and AKI. Restricted cubic spines (RCS) was conducted to explore nonlinear associations between inflammatory biomarkers and AKI. RESULTS: AKI occurred in 53.4% (392/734) of patients, accompanied by significant mortality and length of hospital stay increases in cases of AKI (P < 0.005). After full adjustment of confounders, neutrophil percentage-to-albumin ratio (OR = 0.28), systemic inflammation response index (OR = 0.70), systemic immune inflammation index (OR = 0.69), neutrophil-to-lymphocyte ratio (OR = 0.70), monocyte/high-density lipoprotein cholesterol ratio (OR = 0.53), neutrophil/high-density lipoprotein cholesterol ratio (OR = 0.43) demonstrated an inverse association with AKI. Sensitivity analyses revealed that patients in the highest quartile of these biomarkers exhibited a significantly lower prevalence of AKI compared to those in the lowest quartile (p for trend < 0.05). The RCS analysis suggested an "Inverted U-shaped" association of both LnNPAR and LnSIRI with AKI. CONCLUSIONS: This study identified an inverse association between preoperative inflammatory biomarkers and postoperative AKI in patients with preoperative renal dysfunction. The findings implied that preoperative inflammation may play a protective role against postoperative AKI in this patient population undergoing cardiac surgery.